Content uploaded by Michele Peake Andrasik
Author content
All content in this area was uploaded by Michele Peake Andrasik on Oct 07, 2014
Content may be subject to copyright.
Depressive Symptoms and Cervical Neoplasia
in HIV+ Low-Income Minority Women with Human
Papillomavirus Infection
Stacy M. Dodd &Deidre B. Pereira &Ilona Marion &
Michele Andrasik &Rachel Rose &Trudi Simon &
Mary Ann Fletcher &Joseph Lucci &Kevin Maher &
Mary Jo O’Sullivan &JoNell Efantis-Potter &
Michael H. Antoni
Published online: 8 May 2009
#International Society of Behavioral Medicine 2008
Abstract
Background Prior work has related elevated life stress to
greater risk of cervical neoplasia in women with human
immunodeficiency virus (HIV) and human papillomavirus
(HPV).
Purpose This study investigated associations between
depressive symptoms and cervical neoplasia in HIV+
HPV+ women. Participants were 58 HIV+ HPV+ women.
Method Participants underwent colposcopy, including HPV
screening, Papanicolaou smear, and cervical biopsy to
determine study eligibility. Eligible participants completed
the Beck Depression Inventory (BDI) and the Center for
Epidemiologic Studies-Depression (CES-D) scale.
Results Presence and severity of clinically significant
depressive symptomatology were associated with cervical
neoplasia. Hierarchical logistic regression analysis revealed
that women with greater depressive symptoms had margin-
ally greater odds of presenting with cervical neoplasia
(BDI: OR=1.16, p=0.092; CES-D: OR = 1.15, p= 0.067.
Women with greater somatic depressive symptoms, specif-
ically, had significantly greater odds of presenting with
cervical neoplasia (BDI: OR= 1.86, p= 0.027; CES-D: OR =
1.56, p=0.017).
Conclusion These findings suggest that screening HIV+
women for somatic depression may help identify those at risk
for cervical neoplasia. Future depression research with
medical populations should discern somatic depressive
symptoms from disease symptoms, as they may have
important value in independently predicting health outcomes.
Keywords HIV.Human papillomavirus (HPV) .Cervical
neoplasia .Depressive symptoms .Psychoneuroimmunology
(PNI) .Women
Introduction
HIV and AIDS are serious global health threats. Approxi-
mately 37.8 million people are currently living with HIV/
AIDS and over 20 million have died from the disease since the
epidemic began in 1981 [1]. Although HIV and AIDS are
serious health threats for all Americans, they have a
disproportionately large impact on the African American
community, and specifically on African American women.
Currently, HIV/AIDS is the leading cause of death in African
American women between the ages of 25 and 34 [2].
Int. J. Behav. Med. (2009) 16:181–188
DOI 10.1007/s12529-008-9025-1
S. M. Dodd :D. B. Pereira (*)
Department of Clinical and Health Psychology,
University of Florida,
P.O. Box 100165, Gainesville, FL 32610-0165, USA
e-mail: dpereira@phhp.ufl.edu
I. Marion :M. H. Antoni
University of Miami,
Coral Gables, FL, USA
M. Andrasik
University of Washington,
Seattle, WA, USA
R. Rose
Atlanta Center for Eating Disorders,
Atlanta, GA, USA
T. Simon :M. A. Fletcher :J. Lucci :K. Maher :
M. J. O’Sullivan :J. Efantis-Potter
University of Miami,
Miami, FL, USA
HIV and Human Papillomavirus Infection in Women
Several opportunistic illnesses are more common, harder to
treat, or occur exclusively in women with HIVas compared to
their male counterparts. Examples include disorders of the
upper genital tract, such as pelvic inflammatory disease, as
well as disorders of the lower genital tract, such as cervical
intraepithelial neoplasia (CIN; [3]. CIN is the premalignant
phase of cervical cancer that is initiated and promoted to
cervical cancer by oncogenic or high-risk (HR) Human
Papillomaviruses (HPVs) including HPV 16 and 18 infec-
tions. Among immunocompetent women with HPV infec-
tion, adequate innate and cell-mediated immune responses,
most notably T helper type 1 (Th1) cell immune responses,
will eradicate the virus before it promotes the premalignant
or malignant transformation of cells [4]. However, HPV-
infected women with suppressed cellular immune responses,
such as women with immunodeficiency due to HIV
infection, are often unable to mount an adequate immune
defense against HPV, resulting in persistent and severe HPV
infection and risk for malignant transformation of cells.
Other risk factors for CIN and cervical cancer among women
with HIV include degree of immunosuppression (low T
helper–inducer lymphocyte [CD4+CD3+] cell counts; [5],
tobacco smoking [6], and uncontrolled HIV viral load [5].
Psychoneuroimmunologic Associations in HIV+ Women
at Risk for Neoplasia
Research investigating psychosocial variables and the
presence and/or persistence of CIN has yielded inconsistent
results. Previous research has shown that poorer psycho-
logical well-being (greater pessimistic attitude, greater
negative life event stress) is associated with lower cell-
mediated and natural immunity [7], greater number of
genital herpes recurrences [8], and greater odds of
progression and/or persistence of cervical neoplasia [9]in
women with HIV and HPV infections. In contrast, other
researchers have reported no associations between CIN
progression or regression with negative life events, lack of
social support, or coping style [10]. No research to date has
explored whether other common and treatable psycholog-
ical conditions, such as depression, are associated with
cervical neoplasia in women with HIV and HPV infections.
This may be important to examine for several reasons.
Depressive symptoms are common among individuals with
HIV infection, with nearly half of HIV+ individuals
meeting criteria for depression [11] and nearly twice as
many HIV+ women experiencing depression than HIV+
men [12]. In addition, there is evidence to suggest that
depression may have a significant health impact on HIV+
individuals via a more rapid decline of CD4+CD3+ cell
counts, decreased natural killer cell activity, increased HIV
viral load, faster development of any AIDS-defining condi-
tion, and greater risk of HIV-related mortality (e.g., 13–16).
In spite of this research, associations between depression
and the pathogenesis of specific AIDS-related infections or
neoplasias such as CIN has not yet been explored. The
purpose of the current study was to determine whether
recent depressive symptoms were associated with the
presence of cervical neoplasia in a sample of primarily
black women with HIV infection, a population in which
there has been relatively little published biobehavioral
research. It was hypothesized that women with greater
recent depressive symptomatology would have greater odds
of cervical neoplasia at study entry.
Methods
Participants
Participants for this study were recruited through an
obstetric and gynecology clinic providing care to women
with HIV infection at a large academic medical center in the
southeastern US as part of a longitudinal National-Cancer-
Institute-funded center grant (P50 CA 084944-05). Inclu-
sion criteria were: (a) HIV+ women ages 18 to 60 years old,
(b) history of at least two Papanicolaou smears indicating
low-grade squamous intraepithelial lesions (SIL) or two
cervical biopsies indicating CIN I in the 2 years prior to study
entry, and (c) fluency in spoken English. Exclusion criteria
were: (a) two or more negative Papanicolaou smears in the
2 years prior to study entry, (b) any history of high-grade SIL
or any history of CIN II, CIN III, or invasive cervical cancer,
(c) any diagnostic or treatment procedures for CIN in the
6 months prior to study entry, (d) life expectancy less than
12 months as determined by the study’s research nurse, and
(e) current major severe psychiatric illnesses that would
interfere with the ability to provide valid psychosocial
assessment data (e.g., suicidality, psychoticism, HIV demen-
tia). Potentially eligible women were identified by the
study’s research nurse (a nurse practitioner who provided
clinical care to patients in the obstetric and gynecology
clinic) by reviewing the clinic’s internal database of cervical
cytology results. Potentially eligible women were then
contacted by phone or in person at routine or problem-based
clinic visits to introduce the study. All participants signed a
University of Miami Institutional-Review-Board-approved
informed consent form to indicate their willingness to
participate in this research.
Procedures
Detection of CIN Participants underwent a colposcopic
examination at study entry according to standard colpo-
182 Int. J. Behav. Med. (2009) 16:181–188
scopy protocol, which was comprised of a Papanicolaou
smear and, if medically indicated, colposcopic-guided
cervical biopsy. Cervical biopsies were not performed on
13 women for whom biopsy was medically contraindicated.
Based on the resulting histology and cytology reports,
participants were classified as being positive or negative for
CIN at study entry.
Assessment of Depressive Symptoms Once eligibility was
established, participants were notified of both their results
and study eligibility by the study’s research nurse.
Participants were then scheduled to undergo a face-to-face
psychosocial assessment within approximately 4 to 6 weeks.
The psychosocial assessment consisted of a 60–90-min
psychosocial interview to assess life stress, mood, and
health behaviors. Depressive symptoms were assessed
during this interview using the Beck Depression Inventory
(BDI; [17]) and the Center for Epidemiologic Study-
Depression (CES-D, [18]) scale, both of which have been
used extensively to measure depression in HIV+ individu-
als (e.g., [19]). The BDI contains 21 questions and assesses
both cognitive–affective and somatic depressive symptoms
over the prior week. The CES-D contains 20 items and is
comprised of four subscales: positive affect, negative affect,
somatic, and interpersonal [20].
Assessment of Potential Biobehavioral Covariates To assess
and control for the degree to which depressive symptoms
may have been associated with cervical health-related
distress, we administered a slightly modified version of
the Psychosocial Effects of Abnormal Pap Smears Ques-
tionnaire (PEAPS-Q; [21]). The PEAPS-Q is a 14-item self-
report instrument measuring distress related to undergoing
colposcopic examination and the possibility of having HPV
or cervical cancer. Given that life stress has been found to
be associated with SIL in prior research with HIV+ women
[8,9], we also assessed and controlled for recent non-CIN-
related life stress using an abbreviated ten-item version of
the Life Events Survey [22] described in detail elsewhere
[8,9]. Total pack-years of smoking, CD4+CD3+ cell
counts, plasma HIV viral load, and presence of HR-HPV
types were also assessed and investigated as potential
covariates [5,6,23]. Hybrid Capture II assay (Digene
Corporation, Gaithersburg, MD, USA) was used to detect
and subtype HR-HPV subtypes.
Statistical Analyses
Descriptive statistics were first computed followed by the
examination of relations between potential demographic
and biobehavioral control variables and cervical neoplasia.
We then examined the relationship between degree of
recent depressive symptoms and category of depressive
symptoms and the presence of cervical neoplasia using
hierarchical logistic regression and Goodman-Kruskal
Gamma measures of association, respectively. The logistic
regression equations contained two blocks of predictor
variables: the first block consisted of biobehavioral risk
factors that were significantly related to cervical neoplasia
in this sample, and the second block consisted of our
psychosocial predictor of interest—total scores on the BDI
and CES-D, as well as scores for the two BDI and four
CES-D subscales. The criterion in all equations was
presence or absence of cervical neoplasia at study entry.
When depression scores were examined as ordinal varia-
bles, Gamma coefficients were computed.
Results
Demographics and Health Status
Seventy-six women were enrolled in this study. The results
reported here are based on 58 participants who provided full
psychosocial, colposcopic, and immune data at study entry.
Results of ttests and chi-square analyses revealed that these
58 participants did not differ significantly from those who
had incomplete data in age, yearly income, years of
education, race–ethnicity, marital status, presence of neo-
plasia or HR-HPV infection, HIV disease status–stage, or
CD4+CD3+ cells per cubic millimeter (p’s>0.05). Demo-
graphic information and indicators of health status among
these women at study entry are summarized in Table 1.
Health Behaviors
Most participants (72%) were taking highly active antiretro-
viral therapy (HAART) at the time of study entry. Self-
reported adherence to HAART was negatively correlated with
HIV viral load, r=−0.44, p=0.004. Of the women who
reported a history of smoking (N=22), pack-years of
smoking ranged from six to 5,110 (M=1,895, SD= 1,867).
Depressive Symptoms
Possible scores on the BDI range from 0 to 63, with higher
scores indicating more depressive symptoms reported.
According to the published manual, BDI scores of 0–13
indicate minimal depression; 14–19 indicate mild depression;
20–28 indicate moderate depression, and 29–63 indicate
severe depression [24]. Participants in this study scored
between 0 and 44 on the total BDI, with a mean of 8.7 (SD=
9.78). Forty-eight women (83%) scored in the minimal
depression range; four women (7%) scored in the mild
depression range; two women (3%) scored in the moderate
Int. J. Behav. Med. (2009) 16:181–188 183
depression range, and four women (7%) scored in the severe
depression range on the BDI. Possible scores on the CES-D
range from 0 to 60, with higher scores indicating more
depressive symptoms reported. Participants in this study
scored between 0 and 45 on the total CES-D, with a mean of
12.9 (SD=10.8). Seventeen women (29.3%) had scores of
16 or above (the traditional cutoff score) on the CES-D.
Relations among Depressive Symptoms, Cervical
Health-Related Distress, Life Stress, Immune Status,
and Health Behaviors
A (partial) Pearson correlation coefficient was calculated to
examine the association between depression scores and
PEAPS-Q scores partialling out number of weeks elapsed
between notification of neoplasia and assessment of
depressive symptoms. There were no significant relation-
ships between PEAPS-Q scores and BDI total and subscale
scores or CES-D total and subscale scores (p’s> 0.10). This
suggests that depressive symptoms at the time of psycho-
social assessment were unrelated to cervical health-related
distress. Women with greater total BDI, cognitive–affective
BDI, and somatic BDI scores reported significantly greater
impact of non-CIN-related negative life events in the prior
6 months, r=0.468, p=0.001; r=0.401, p=0.004, and r=
0.507, p<0.001, respectively. Neither total CES-D nor the
CES-D subscale scores were significantly related to
negative life events. There were no significant correlations
between BDI total and subscale scores or CES-D total and
subscale scores and self-reported adherence to HAART
among women who were taking HAART (n=42; p’s>
0.10). Of the total and subscale scores on the BDI and CES-
D, greater somatic BDI scores were significantly related to
lower CD4+CD3+cell counts, r=−0.298, p= 0.023, as well
as greater HIV viral load, r=0.303, p=0.021. There were
no significant differences on BDI or CES-D scores by HIV
disease status–clinical axis (asymptomatic, symptomatic, or
AIDS; p’s> 0.10).
Relations Among Potential Demographic
and Biobehavioral Control Variables and Neoplasia
Chi-square and logistic regression analyses were conducted
to determine whether potential demographic control varia-
bles (age, income, education, marital status, and race–
ethnicity) were related to cervical neoplasia in this sample.
Results of these analyses demonstrated no significant
relationships between these demographic variables and
cervical neoplasia. Thus, demographic variables were not
included in further analyses as control variables.
Correlational and chi-square analyses were conducted to
determine whether variables that have been shown to be
risk factors for cervical carcinogenesis in HIV+ women
(HIV viral load, HIV disease status–clinical axis, presence
of HR-HPV subtypes, CD4+CD3+ cell counts, and tobacco
smoking) were related to cervical neoplasia in this sample.
Of these, only greater HIV viral load (r= 0.30, p= 0.024)
and presence of HR-HPV subtypes (χ
2
[1]=4.14, p=0.042)
were significantly related to the presence of neoplasia.
Neither life stress nor PEAPS-Q scores was related to
cervical neoplasia in this sample (p> 0.05). HIV viral load
and presence of HR-HPV were entered into block 1 of the
regression equations as control variables.
Relation Between Depressive Symptomatology
and Cervical Neoplasia
There was a perfect positive relationship between greater
clinical severity of BDI depressive symptomatology (i.e.,
minimal, mild, moderate, severe) and presence of cervical
neoplasia, γ=1.0, p=0.004 (Table 2). Furthermore, there
Table 1 Sample characteristics
Number Percent
Demographics
Age (years) 18–24 22 37.9
25–31 11 19.0
32–38 11 19.0
39–45 14 24.1
Race–ethnicity Black–African
American
50 86.2
Hispanic 5 8.6
Caucasian 2 3.5
Other 1 1.7
Marital status Single–never married 32 55.1
Married 13 22.4
Separated–divorced 11 19.0
Widowed 2 3.5
Education Less than high school 22 37.9
Graduated high school 29 50.0
Some college 6 10.3
Income ($/year) 0–10,000 31 53.3
10,001–20,000 18 31.0
20,001–30,000 7 12.0
30,001–40,000 1 1.7
Health status
Cervical neoplasia Present 47 81.0
Absent 11 19.0
High-risk human
papillomavirus Infection
(HR-HPV)
Present 45 77.6
Absent 13 22.4
HIV clinical axis A (Asymptomatic) 23 40.0
B (Symptomatic) 15 25.9
C (AIDS) 19 32.8
CD4+CD3+
(cells per cubic
millimeter)
0–200 9 15.5
201–500 29 50.0
501+ 20 34.5
184 Int. J. Behav. Med. (2009) 16:181–188
was a marginally significant relationship between total BDI
scores and odds of presenting with neoplasia, OR = 1.16,
95% CI=0.975–1.389, p=0.092. There was no significant
relationship between BDI cognitive–affective scores and
odds of cervical neoplasia, OR = 1.146, 95% CI = 0.94–1.4,
p=0.183. However, women with greater BDI somatic
depressive symptomatology had significantly greater odds
of cervical neoplasia, OR=1.86, 95% CI=1.07–3.22, p=
0.027. The logistic regression model predicting cervical
neoplasia from BDI somatic depressive scores while
controlling for HIV viral load and presence of high-risk
HPV was significant, χ
2
(3)=14.96, p=0.002. This signif-
icant relationship remained after additionally controlling for
non-CIN-related life events and distress associated with
colposcopy and the possibility of having HPV–CIN, OR =
2.37, 95% CI=1.11–5.05, p=0.025 (Table 3).
Similar results emerged using the CES-D as a measure of
depressive symptomatology. There was a significant rela-
tionship between clinically significant depressive symp-
tomatology on the CES-D and presence of cervical
neoplasia at study entry, γ=0.675, p= 0.041 (Table 4). In
addition, there was a marginally significant relationship
between total CES-D scores and odds of presenting with
cervical neoplasia, OR=1.15, 95% CI=0.99–1.34, p=
0.067. The logistic regression model predicting cervical
neoplasia from CES-D scores while controlling for HIV
viral load and presence of HR-HPV was significant, χ
2
(3)=
12.92, p=0.005. There were no significant relationships
between odds of cervical neoplasia and CES-D positive
affect, negative affect, or interpersonal scores (all p’s>
0.05). However, similar to the results using the BDI,
women with higher scores on the CES-D somatic subscale
had significantly greater odds of presenting with cervical
neoplasia at study entry, OR= 1.56, 95% CI = 1.08–2.25, p=
0.017. The logistic regression model predicting cervical
neoplasia from scores on the CES-D somatic subscale while
controlling for HIV viral load and high-risk HPV was
significant, χ
2
(3)=16.33, p=0.001. This significant rela-
tionship remained after controlling for life stress and
colposcopic–cervical neoplasia distress, OR = 1.59, 95%
CI=1.01–2.51, p=0.044 (Table 5).
Discussion
Previous research has shown that depression and depressive
symptoms are associated with negative health outcomes for
individuals with HIV infection. However, very little
Table 2 Frequency of women with cervical neoplasia by clinical severity of depressive symptoms as measured by the Beck Depression Inventory
(BDI)
Clinical severity of depressive symptoms
Minimal Mild Moderate Severe Total
Neoplasia status
Neoplasia absent 11 0 0 0 11
Neoplasia present 37 4 2 4 47
Total 48 4 2 4 58
There was a perfect positive relationship between greater clinical severity of BDI depressive symptomatology (i.e., minimal, mild, moderate,
severe) and presence of cervical neoplasia, γ=1.0, p=0.004
Table 3 Predicting cervical neoplasia from depressive symptoms on the Beck Depression Inventory (BDI)
(Step number) predictor βWald statistic Odds ratio pvalue 95% CI
Lower Upper
(1) Biological variables
High-risk HPV 0.95 1.53 2.57 0.22 0.58 11.50
HIV viral load (cells per cubic millimeter [log
10
-transformed]) 0.63 2.92 1.87 0.09 0.91 3.82
(2) Psychological predictor
Eq. 1, total BDI score 0.15 2.84 1.16 0.09 0.98 1.39
Eq. 2, cognitive–affective score 0.14 1.77 1.45 0.18 0.94 1.40
Eq. 3, somatic score
a
0.62 4.87 1.86 0.03 1.07 3.22
N=58. BDI variables entered into block 2 in three separate hierarchical logistic regression equations. Model for Eq. 1 using total BDI, χ
2
(3)=
12.02, p=0.007. Nagelkerke R
2
=0.30; Model for Eq. 2 using cognitive–affective subscale, χ
2
(3)= 10.05, p= 0.018. Nagelkerke R
2
=0.26; Model
for Eq. 3 using somatic subscale, χ
2
(3)= 14.96, p= 0.002. Nagelkerke R
2
=0.37
a
Odds ratio remained significant after additionally controlling for recent negative life stress and distress associated with colposcopic examination
and the possibility of having cervical neoplasia, OR=2.37, 95% CI= 1.11–5.05, p= 0.03.
Int. J. Behav. Med. (2009) 16:181–188 185
research has investigated the possible relationship between
depressive symptoms and HIV-specific disease processes in
women. This is a significant gap in the literature because
the relationship between depression and specific HIV
disease outcomes may help to explain the associations that
have already been demonstrated between depression and
more global outcomes, such as HIV progression and
mortality. By identifying the specific disease processes that
may underlie the previously demonstrated link between
depression and HIV progression and mortality, specific
screening and interventions can be tailored to provide the
most effective and comprehensive treatments for HIV+
women.
The current study is the first to examine the relationship
between depressive symptoms and cervical neoplasia in
HIV+ women. Presence and severity of clinically signifi-
cant depressive symptomatology was associated with
presence of cervical neoplasia at study entry in our sample.
Greater total BDI and CES-D scores were marginally
associated with cervical neoplasia in this sample. Although
there was no significant relationship between the cognitive–
affective, positive or negative affect, or interpersonal
symptoms of depression and cervical neoplasia; greater
levels of somatic depressive symptoms as measured by both
the BDI and the CES-D were significantly associated with
greater odds of cervical neoplasia. This finding persisted
after controlling for recent negative life event stress, a
factor associated with the progression and/or persistence of
cervical neoplasia in our prior research [8,9].
The results of the present study may be especially
significant given research suggesting that both women and
African Americans tend to present frequently with somatic
depressive symptoms, including disturbances in appetite
and sleep [25,26]. Similarly, some research with HIV+
individuals suggests that fatigue and insomnia are frequent
manifestations of depression rather than HIV disease status
[27]. The results of the present research are consistent with
one large-scale longitudinal study that demonstrated that
somatic depressive symptoms were associated with pro-
gression to AIDS, progression to HIV dementia, and
Table 4 Frequency of women with cervical neoplasia by presence of clinically significant depressive symptoms as measured by the Center for
Epidemiologic Studies-Depression (CES-D) scale
Presence of clinically significant depressive symptoms
Not depressed Depressed Total
Neoplasia status
Neoplasia absent 10 1 11
Neoplasia present 31 16 47
Total 41 17 58
There was a significant relationship between presence of clinically significant depressive symptomatology on the CES-D and presence of cervical
neoplasia at study entry, γ=0.675, p= 0.041
Table 5 Predicting cervical neoplasia from depressive symptoms on the Center for Epidemiologic Studies-Depression (CES-D) scale
(Step number) predictor βWald statistic Odds ratio Pvalue 95% CI
Lower Upper
(1) Biological variables
High-risk HPV 0.95 1.53 2.57 0.22 0.58 11.50
HIV viral load (cells per cubic millimeter [log
10
-transformed]) 0.63 2.92 1.87 0.09 0.91 3.82
(2) Psychological predictor
Eq. 1, total CES-D score 0.14 3.36 1.15 0.07 0.99 1.34
Eq. 2, positive affect score 0.17 1.53 1.18 0.22 0.91 1.55
Eq. 3, negative affect score 0.11 1.18 1.12 0.28 0.91 1.37
Eq. 4, interpersonal score 1.31 1.48 3.70 0.22 .45 30.47
Eq. 4, somatic score
a
0.45 5.73 1.56 0.02 1.08 2.25
N=58. CES-D variables entered into block 2 in five separate hierarchical logistic regressions. Model for Eq. 1 using total CES-D, χ
2
(3)= 12.92,
p=0.005. Nagelkerke R
2
=0.32; Model for Eq. 2 using positive affect subscale, χ
2
(3)= 8.86, p= 0.03. Nagelkerke R
2
=0.23; Model for Eq. 3
using negative affect subscale, χ
2
(3)= 8.69, p= 0.03. Nagelkerke R
2
=0.22; Model for Eq. 4 using Interpersonal subscale, χ
2
(3)= 10.38, p= 0.02.
Nagelkerke R
2
=0.26; Model for Eq. 5 using somatic subscale, χ
2
(3)= 16.33, p= 0.001. Nagelkerke R
2
=0.40
a
Odds ratio remained significant after additionally controlling for recent negative life stress and distress associated with colposcopic examination
and the possibility of having cervical neoplasia, OR=1.59, 95% CI= 1.01–2.51, p= 0.04
186 Int. J. Behav. Med. (2009) 16:181–188
shortened survival [28]. This body of research suggests that
somatic depression may be an important marker of
depressive disorders and a significant correlate of clinical
health status in HIV+ individuals.
Caution must be used when interpreting our findings
given our modest sample size, undersampling of severely
depressed women, and cross-sectional design, the latter of
which precludes the ability to establish whether somatic
depression causes cervical neoplasia or vice versa. Of note,
the BDI and CES-D were administered to participants after
they had been notified of their Papanicolaou smear and
cervical biopsy results. Although this raises some concern
that BDI results may be confounded with CIN-related
distress, an examination of BDI and PEAPS-Q scores
demonstrated that there was no association between distress
related to the colposcopy and depressive symptoms.
Although this may have restricted the degree to which
health-related distress may have been confounded with
depression, only prospective studies can shed light on
whether depressive symptoms actually forecast differences
in CIN promotion in this population. Because some women
were recruited during routine or problem-based medical
visits, an unavoidable selection bias may have occurred, as
women who were more severely depressed or who had
more advanced HIV disease may have been less likely to
access this type of medical care. An additional limitation is
that several participants did not have a cervical biopsy
performed due to the presence of clinical contraindications
for biopsy. A cervical biopsy is necessary to establish a
diagnosis of cervical neoplasia, and it is possible that
cervical cytology may have underestimated the degree of
cervical neoplasia present among these participants.
Future research should utilize prospective, longitudinal,
and/or experimental designs to facilitate the examination of
possible causal mechanisms between depressive symptoms
and cervical neoplasia. Somatic depression may be associ-
ated with greater odds of cervical neoplasia through
impaired immune functioning (e.g., shift in the production
of cytokines from a pattern that promotes cellular immunity
to one that promotes primarily humoral immunity; [29]or
through nonadherence to medical regimens, such as
Papanicolaou smear screening and HAART use. Future
research should be guided by a model that would allow the
testing of multiple mediators of the relationship between
somatic depression and cervical neoplasia, including both
cytokine production and health behaviors and bidirectional
relationships among these variables.
The findings of this study suggest that it may be
important to assess the presence and severity of depressive
symptoms, including somatic symptoms, among HIV+
women. The identification and treatment of depression
among HIV+ HPV+ women may enhance health-related
quality of life in part via reduction in risk of cervical cancer.
Acknowledgement This research was supported by the National
Cancer Institute (P50 CA 084944-05, PI, Michael H. Antoni,
Ph.D.).
References
1. Joint United Nations Programme on HIV/AIDS. 2004 report on
the global AIDS epidemic: 4th global report. Geneva: UN; 2004.
2. Anderson RN, Smith BL. Deaths: leading causes for 2002. Natl
Vital Stat Reports 2005;53:67–70.
3. Center for Disease Control and Prevention. 1993 revised
classification system for HIV infection and expanded surveillance
case definition for AIDS among adolescents and adults.1992;41:
RR–17.
4. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsaque X,
Shah KV, et al. Epidemiologic classification of human papilloma-
virus types associated with cervical cancer. N Engl J Med
2003;348:518–27.
5. Davis AT, Chakraborty H, Flowers L, Mosunjac MB. Cervical
dysplasia in women with the human immunodeficiency virus
(HIV): a correlation with HIV viral load and CD4+ count.
Gynecol Oncol 2001;80:350–4.
6. Hocke C, Leroy V, Morlat P, Rivel J, Duluc MC, Boulogne N,
Tandonnet B, Dupon M, Brun JL, Dabis F. Cervical dysplasia and
human immunodeficiency virus infection in women: prevalence
and associated factors. Eur J Obstet Gynecol Reprod Biol
1998;81:69–76.
7. Byrnes DM, Antoni MH, Goodkin K, Efantis-Potter J, Asthana D,
Simon T, et al. Stressful events, pessimism, natural killer cell
cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black
women at risk for cervical cancer. Psychosomatic Medicine
1998;60:714–22.
8. Pereira DB, Antoni MH, Danielson A, Simon T, Efantis-Potter J,
Carver CS, Duran RE, Ironson G, Klimas N, Fletcher MA,
O’Sullivan MJ. Stress as a predictor of symptomatic genital
herpes virus recurrence in women with human immunodeficiency
virus. J Psychosom Res 2003a;54:237–44.
9. Pereira DB, Antoni MH, Danielson A, Simon T, Efantis-Potter J,
Carver CS, Duran RE, Ironson G, Klimas N, O’Sullivan MJ. Life
Stress and cervical squamous intraepithelial lesions in women
with human papillomavirus and human immunodeficiency virus.
Psychosom Med 2003b;65:427–34.
10. Tiersma ESM, van der Lee ML, Garssen B, Peters AAW, Visser
AP, Fleuren GJ, et al. Psychosocial factors and the course of
cervical intra-epithelial neoplasia: a prospective study. Gynecol
Oncol 2005;97:879–86.
11. Chandra PS, Ravi V, Desai A, Subbakrishna DK. Anxiety and
depression among HIV-infected heterosexuals—a report from
India. J Psychosom Res 1998;45:401–9.
12. Evans DL, Ten Have TR, Douglas SD, Gettes DR, Morrison M,
Chiappini MS, et al. Association of depression with viral load,
CD8 T lymphocytes, and natural killer cells in women with HIV
infection. Am J Psychiatr 2002;159:1752–9.
13. Ickovics JR, Hamburger ME, Vlahov D, Schoenbaum EE,
Schuman P, Boland RJ, HIV Epidemiology Research Study
Group, et al. Mortality, CD4 cell count decline, and depressive
symptoms among HIV-seropositive women: longitudinal analysis
from the HIV Epidemiology Research Study. J Am Med Assoc
2001;285:1466–74.
14. Leserman J, Petitto JM, Gu H, Gaynes BN, Barroso J, Golden
RN, et al. Progression to AIDS, a clinical AIDS condition, and
mortality: psychosocial and physiological predictors. Psychol Med
2002;32:1059–73.
Int. J. Behav. Med. (2009) 16:181–188 187
15. Sahs JA, Goetz R, Reddy M, Rabkin JG, Williams JB, Kertzner R,
et al. Psychological distress and natural killer cells in gay men with
and without HIV infection. Am J Psychiatry 1994;151:1479–84.
16. Vedhara K, Schifitoo G, McDermott M. Disease progression in HIV-
positive women with moderate to severe immunosuppression: the
role of depression. Dana Consortium on Therapy for HIV Dementia
and Related Cognitive Disorders. Behav Med 1999;25:43–7.
17. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory
for measuring depression. Arch Gen Psychiatry 1961;4:561–71.
18. Radloff LS. The CES-D scale: a self-report depression scale for
research in the general population. Appl Psychol Meas
1977;1:385–401.
19. Weiser SD, Riley ED, Ragland K, Hammer G, Clark R,
Bangsberg DR. Brief report: factors associated with depression
among homeless and marginally housed HIV-infected men in San
Francisco. J Gen Intern Med 2006;21:61–4.
20. Sheehan TJ, Fifield J, Reisine S, Tennen H. The measurement
structure of the Center for Epidemiologic Studies Depression
Scale. J Pers Assess 1995;64:507–21.
21. Bennetts A, Irwig L, Oldenburg B, Simpson JM, Mock P, Boyes A, et
al. PEAPS-Q: a questionnaire to measure the psychosocial effects of
having an abnormal pap smear. J Clin Epidemiol 1995;48:1235–43.
22. Sarason IG, Johnson JH, Siegel JM. Assessing the impact of life
change: development of the Life Experiences Survey. J Consult
Clin Psychol 1978;46:932–46.
23. Phelps RM, Smith DK, Heilig CM, Gardner LI, Carpenter CC,
Klein RS, Jamieson DJ, Vlahov D, Schuman P, Holmberg SD.
Cancer incidence in women with or at risk for HIV. Int J Cancer
2001;94:753–7.
24. Beck AT, Steer RA, Brown GK. Manual for the beck depression
inventory, 2nd ed. San Antonio: Psychological Corporation; 1996.
25. Das AK, Olfson M, McCurtis HL, Weissman MM. Depression in
African Americans: breaking barriers to detection and treatment. J
Fam Pract 2006;55:30–9.
26. Silverstein B. Gender differences in the prevalence of somatic
versus pure depression: a replication. Am J Psychiatry 2002;159:
1051–2.
27. Perkins DO, Leserman J, Stern RA, Baum SF, Liao D, Golden
RN, et al. Somatic symptoms and HIV infection: relationship to
depressive symptoms and indicators of HIV disease. Am J
Psychiatr 1995;152:1776–81.
28. Farinpour R, Miller EN, Staz P, Selnes OA, Cohen BA, Becker
JT, et al. Psychosocial risk factors of HIV morbidity and
mortality: findings from the Multicenter AIDS Cohort Study
(MACS). J Clin Exp Neuropsychol 2003;25:654–70.
29. Bais AG, Beckmann I, Lindemans J, Ewing PC, Meijer
CJLM, Snijders PJF, et al. A shift to a peripheral Th2-type
cytokine pattern during the carcinogenesis of cervical cancer
becomes manifest in CIN III lesions. J Clin Pathol 2006;58:
1096–100.
188 Int. J. Behav. Med. (2009) 16:181–188
